Creutzfeldt-Jakob disease (CJD) is the commonest form of human prion disease and occurs in sporadic, genetic and acquired forms. The causative agents (prions) appear to be composed entirely of a modified host protein, the prion protein, which undergoes misfolding to a disease-associated isoform closely associated with infectivity that is resistant to conventional methods of decontamination. Prions can be transmitted from one individual to another by medical and surgical procedures, resulting in iatrogenic CJD (iCJD). The commonest cause of iCJD is the inoculation of cadaveric pituitary-derived human growth hormone (hGH) to treat growth hormone deficiency in children; this form of treatment was abandoned in 1985 after the first UK case of iCJD in a hGH recipient was identified. Seventy-eight cases of iCJD have since occurred in the UK cohort of 1849 hGH recipients, including a case in 2016. This thesis describes a comprehensive tissue-based and molecular genetic analysis of the largest series (35 cases) of UK hGH-iCJD cases reported to date, including in vitro kinetic molecular modelling of genotypic factors influencing prion transmission. The results show that the polymorphism at codon 129 of the prion protein gene strongly influences the disease incubation period in hGH-iCJD (from 7.8-32.3 years in this series) and interacts with the infectious prion strain to govern the molecular and pathological characteristics of iCJD. The findings are consistent with the hypothesis that the UK hGH-iCJD epidemic resulted from transmission of the V2 human prion strain, which is found in the second most common form of sporadic CJD. The investigation also found accumulation of the amyloid beta (Aβ) protein associated with Alzheimer’s disease (AD) in the brains and cerebral blood vessels in 18/35 hGH-iCJD patients and 5/12 control patients who had been treated with hGH, but died from causes other than iCJD. In contrast, Aβ accumulation was markedly less prevalent in age-matched patients who died from sporadic CJD (1/15 cases) and variant CJD (2/33 cases). These results are consistent with the hypothesis that Aβ, which can accumulate in the pituitary gland, was present in the inoculated hGH preparations and seeded into the brains of around 50% of all hGH recipients, producing AD-like neuropathology and cerebral amyloid angiopathy (CAA). This provides further evidence of the prion-like properties of Aβ and gives insight into the potential for possible transmission of AD/CAA. It is uncertain whether any Aβ seeding within the brains of surviving patients in the UK hGH recipient cohort will ultimately result in clinical AD; however, the CAA in these patients may be complicated by intracerebral haemorrhage resulting from rupture of the blood vessels damaged by Aβ accumulation within their walls.

The aerodynamic team at SCANIA has discovered the need to investigate the effect of the upstream turbulence conditions on the aerodynamics of the trucks. This need comes from the fact that there are differences between the drag coefficients obtained using computational fluid dynamics (CFD) and the on-road measurements. This difference can lead to wrong predictions of fuel consumption and emissions, which can cause incorrect evaluation of design changes. In this study the problem of modeling upstream turbulence in CFD simulations is addressed together with its effect on the aerodynamics of the trucks. To achieve this, representative values of turbulence intensity and length scale were found from the work of different researchers, who performed on-road measurements for various conditions. These values were then used in a method by Jakob Mann to generate a synthetic turbulence field. This field was then used to generate time varying velocity components, added to the mean velocity at the inlet of a CFD simulation. After the implementation of the method it was discovered that the conditions at the test section of the virtual wind tunnel were representative of the on-road measurements. The results showed drag increase and wake length decrease, similar to previous studies performed on simple geometries. It also showed that the higher mixing of the flow increases the drag by surface pressure increase of forward facing surfaces and pressure decrease at the base. These conclusions may be extended to other bluff body geometries and it shows the importance of good design around gaps. The comparison between two truck geometries showed that a truck with better aerodynamics in a smooth flow shows less drag increase with introduction of upstream turbulence.

One of the key molecular events in the transmissible spongiform encephalopathies or prion diseases is the conformational conversion of the cellular prion protein PrPC into the misfolded and pathogenic isoform, PrPSc. Prion diseases are fatal neurodegenerative conditions affecting humans and other animal species, which present with diverse clinical and neuropathological phenotypes. In humans, prion diseases can occur as sporadic, familial or acquired forms. Sporadic Creutzfeldt–Jakob disease (sCJD) accounts for the majority of cases. The current classification system of human prion diseases recognizes several distinct clinico-pathological entities including sCJD, variant Creutzfeldt-Jakob disease (vCJD), Gerstmann–Straussler–Scheinker syndrome, fatal familial insomnia and variably protease-sensitive proteinopathy. Prion protein gene (PRNP) mutations and polymorphisms, and PrPSc types have a profound effect on these clinico-pathological phenotypes. Prion diseases of sheep and goats, cattle, and cervids are all actual animal health problems and present potential risks to human health. Thus far the only known zoonotic prion disease is bovine spongiform encephalopathy, which has resulted in vCJD in humans. The recognition of new forms of prion diseases in animal and humans has generated increased awareness of the animal and public health risks associated with prion disease. However the mechanisms involved in prion replication, transmission, and neurodegeneration remain poorly understood. This thesis uses in vitro PrP conversion assays (protein misfolding cyclic amplification and real time quaking-induced conversion) to model different aspects of human prion replication: Molecular susceptibility, genetic compatibility, spontaneous formation and the effect of molecules that might enhance or prevent conversion were each investigated in order to obtain a better understanding of the molecular mechanism of the prion replication. I have addressed the hypothesis that the major determinant factors in prion disease pathogenesis (PRNP genetics, PrPSc types and species barriers) are intrinsic to the prion protein conversion process and their effects can be faithfully recapitulated by in vitro conversion assays. The results shows that in vitro conversion assays used in this thesis can model the combined effects of different PrP type and genotypes, can replicate aspects of cross-species transmission potential and provide information about molecular barrier to zoonotic transmission, can model de novo PrPSc formation, and can assess the potential impact of chaperones on conversion of the human prion protein. In summary, this work provides evidence that the origin, propagation and transmission of prions can be meaningfully investigated in cell-free systems.

This thesis is based on eleven Storm and Stress dramas of Lenz and Kllnger. It discusses extensively the lack of freedom of their Storm and Stress characters in the society of the day, as seen in the dramas, and also examines these characters' search for freedom and the meaning they attribute to freedom. In addition, this investigation attempts to establish a concept of ultimate freedom and to show that some "Stürmer und Dränger" possess it and are thereby able to carry out their mission of social improvement while finding individual happiness and fulfillment. The term "Stürmer und Dränger" is used throughout the thesis to mean only the Storm and Stress characters in the plays discussed and does not refer to the writers of this period. / Arts, Faculty of / Central Eastern Northern European Studies, Department of / Graduate

L'histoire standard de la géométrie projective souligne l'opposition au 19e siècle entre méthodes analytiques et synthétiques. Nous nous interrogeons sur la manière dont les géomètres du 19e siècle ont vraiment opéré ou non des distinctions entre leurs méthodes et dans quelle mesure cette géométrie était "moderne'' comme le clamaient ses praticiens, et plus tard leurs historiens. Poncelet insistait sur le rôle central de la figure, qui selon lui pourrait être obscurci par les calculs de l'algèbre. Nous étudions son argument en action dans des problèmes de construction résolus par plusieurs auteurs différents -comme la construction d'une courbe du second ordre ayant un contact d'ordre trois avec une courbe plane donnée, dont cinq solutions paraissent entre 1817 et 1826. Nous montrons que l'attention visuelle est au coeur de la résolution, indépendamment de la méthode suivie, qu'elle n'est pas réservée aux figures, et que les débats sont aussi un moyen de signaler de nouvelles zones de recherche à un public en formation. Nous approfondissons ensuite la réception des techniques nouvelles et l'usage des figures dans les travaux de deux mathématiciens décrits d'ordinaire comme opposés, l'un algébriste, Plücker, et l'autre défendant l'approche synthétique, Steiner. Nous examinons enfin les affirmations de modernité dans les manuels français de géométrie publiés pendant le premier tiers du dix-neuvième siècle. Tant Gergonne et Plücker que Steiner ont développé des formes de géométrie qui ne se pliaient pas en fait à une caractérisation dichotomique, mais répondaient de manière spécifique aux pratiques mathématiques et aux modes d'interaction de leur temps. / The standard history of nineteenth century geometry began with Jean Victor Poncelet's contributions which then spread to Germany alongside an opposition between Julius Plücker, an analytic geometer, and Jakob Steiner, a synthetic geometer. Our questions centre on how geometers distinguished methods, when opposition arose, in what ways geometry disseminated from Poncelet to Plücker and Steiner, and whether this geometry was "modern'' as claimed.We first examine Poncelet's argument that within pure geometry the figure was never lost from view, while it could be obscured by the calculations of algebra. Our case study reveals visual attention within constructive problem solving, regardless of method. Further, geometers manipulated and represented figures through textual descriptions and coordinate equations. We also consider the debates involved as a medium for communicating geometry in which Poncelet and Gergonne in particular developed strategies for introducing new geometry to a conservative audience. We then turn to Plücker and Steiner. Through comparing their common research, we find that Plücker practiced a "pure analytic geometry'' that avoided calculation, while Steiner admired "synthetic geometry'' because of its organic unity. These qualities contradict usual descriptions of analytic geometry as computational or synthetic geometry as ad-hoc.Finally, we study contemporary French books on geometry and show that their methodological divide was grounded in student prerequisites, where "modern'' implied the use of algebra. By contrast, research publications exhibited evolving forms of geometry that evaded dichotomous categorization.The standard history of nineteenth century geometry began with Jean Victor Poncelet's contributions which then spread to Germany alongside an opposition between Julius Plücker, an analytic geometer, and Jakob Steiner, a synthetic geometer. Our questions centre on how geometers distinguished methods, when opposition arose, in what ways geometry disseminated from Poncelet to Plücker and Steiner, and whether this geometry was "modern'' as claimed.We first examine Poncelet's argument that within pure geometry the figure was never lost from view, while it could be obscured by the calculations of algebra. Our case study reveals visual attention within constructive problem solving, regardless of method. Further, geometers manipulated and represented figures through textual descriptions and coordinate equations. We also consider the debates involved as a medium for communicating geometry in which Poncelet and Gergonne in particular developed strategies for introducing new geometry to a conservative audience. We then turn to Plücker and Steiner. Through comparing their common research, we find that Plücker practiced a "pure analytic geometry'' that avoided calculation, while Steiner admired "synthetic geometry'' because of its organic unity. These qualities contradict usual descriptions of analytic geometry as computational or synthetic geometry as ad-hoc.Finally, we study contemporary French books on geometry and show that their methodological divide was grounded in student prerequisites, where "modern'' implied the use of algebra. By contrast, research publications exhibited evolving forms of geometry that evaded dichotomous categorization.

In this thesis I will describe the process of working with a piano trio. The trio consisted of Jonny Ek on piano, Uno Dvärby on bass and, me, Jakob Bylund on drums. This process included choosing musicians, studying influences, rehearsing, and the selecting and arranging songs.  I will also reflect on my role as the drummer and band leader of the trio. The main purpose was to investigate what happens to a trio that does not only rehearse often, but also puts in a lot of work in to studying their role models, such as Oscar Peterson trio and Ahmad Jamal trio, by listening and transcribing arrangements played by them.  By using these methods, the trio hoped to achieve a greater understanding of what these references were actually playing, and using that knowledge to develop its own interplay, dynamics and sound.  The impact of role models is analyzed by comparing the Oscar Peterson trio and Ahmad Jamal trio to each other, and to my own trio, finding the uniqueness of each group as well as the similarities between them.  During this project I have learned a lot as a drummer, arranger and band leader. Because of our many rehearsals and the way we studied our role models, I have gained a deeper understanding of my tendencies when drumming. I’ve also learned that the drummer in a piano trio could determine the direction of the music with very subtle but efficient ways, and therefore has a lot of power and responsibility to take care of the music.  As a result of using these methods the trio managed to get a deeper understanding of why its role models sounded like they did and use that information to develop in their footprints. / <p>Jonny Ek - Piano.</p><p>Uno Dvärby - Kontrabas.</p><p>Jakob Bylund - Trummor.</p><p></p><p>"Where Or When" - Richard Rodgers</p><p>"Long Ago And Far Away" - Jerome Kern</p><p>"Black And Tan Fantasy" - Duke Ellington</p><p>"I Was Doing All Right" - George Gershwin</p><p>"In The Wee Small Hours Of The Morning" - David Mann</p><p>"Avalon" - Al Jolson, Buddy DeSylva, Vincent Rose</p><p>"Con Alma" - Dizzy Gillespie</p><p>"It's Only A Paper Moon" - Harold Arlen</p><p>"Easy Living" - Ralph Rainger</p>

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Användbarhet och användarupplevelser spelar en stor roll för företag på digitala marknaden. Inte minst för mindre företag som anställer en webbyrå som utvecklar hemsidan åt kunden och sedan drivs enskilt av ägaren. Efterfrågan på ett gränssnitt med hög användbarhet har ökat, och att kunna analysera användbarheten på sin egna e-handel på ett effektivt sätt är viktigt för småföretag. Denna studie ska undersöka en kostnads- och tidseffektiv analysmetod för småskaliga e-handelssidor. För att svara på frågeställningen kommer arbetet utgå från två vedertagna analysmetoder som kommer testas på företaget Bernt i Lunds hemsida. Metoderna är Nielsens 10 Heuristiker och Bekker &amp; Merwe’s analysmetod. Dessa kommer sedan utvärderas utifrån antal identifierade problem, typ av problem, generella/e-handelsspecifika problem samt strukturen av metoderna. Detta ligger sedan till grund för en egen framtagen metod som är anpassad till småskaliga e-handelssidor likt Bernt i Lund.  Resultatet börjar med att presentera resultaten från båda metoderna för sig. Bekker &amp; Merwe’s metod gav hemsidan ett helhetsbetyg på 62,25 på en skala -160 till 160. Nielsen’s Heuristiska test lyckades identifiera 52 stycken unika problem på hemsidan. Sedan presenteras det slutgiltiga resultatet i form av en ny analysmetod som är baserad Nielsen’s Heuristiska metod som appliceras på ramverket från Bekker &amp; Merwe’s metod. Den nya metoden testades och lyckades identifiera 109 stycken unika problem på sidan. Slutsatsen vi kan dra är att den nya analysmetoden är mer effektiv för Bernt i Lunds hemsida för att identifiera fler stora och små problem samt tiden det tar att finna problem.

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